A special CRC subtype characterized by a high tumor mutational burden (TMB), more tumor neoantigens, and a higher density of tumor infiltrating lymphocytes.
Mismatch repair deficiency is found in up to 15% of non metastatic colon cancers.
Defects in the DNA mismatch repair machinery can be identified by detecting the loss of MMR protein expression by the use of immunohistochemical analysis, or by detection of microsatellite instability with the use of PCR essays.
These immunogenic features make dMMR CRC highly responsive to treatment with PD-1 blockade.
dMMR CRC is not benefited by neoadjuvant chemotherapy.
PD-1 blockade of dMMR CRC is highly effective with objective response rates in all patients, and 60% achieving pathologic complete response.
100% of patients with localized dMMR rectal cancer achieves a complete remission after six months of treatment PD-1 blockade.
Results of neoadjuvant immunotherapy for localized dMMR CRC show high rates of major and complete pathological response (Emilojou O).
In patients with locally advanced dMMR colon cancer, neoadjuvant nivolumab plus ipilimumab had an acceptable profile and lead to pathological response in a high proportion of patients (Chalabi, M).